The objective of our research program is to search for unique characteristics of human biology which determine the extraordinary human capacity for general health maintenance and longevity as compared to other mammalian species. This research program has been guided by theoretical studies suggesting that a common set of specific longevity determinant genes exists in all mammals. Work has centered on two basic but interrelated areas: (1) determining if the cause of aging is largely the result of dysdifferentiative processes and (2) determining if the rate of aging is governed by mechanisms acting to stabilize the proper differentiated state of cells. With reference to the first area, stability of gene regulation has been investigated by measuring the steady state levels of mRNA for the genes coding for the endogenous retroviruses, oncogenes and satellite heterochromatin DNA as a function of age in a number of tissues from mice and human. With reference to the second area of research, we have been investigating if oxidative stress may be a primary cause of aging, acting to destabilize the proper differentiated state of cells. Methods are currently being developed to measure specific products of oxidation of DNA and protein using GC/MS, HPLC and monoclonal antibody (ELISA) techniques.